The structure-activity relationship analysis has been performed for trans- and cis-hydroxycinnamic acids, to determine their theoretical antioxidant pharmacophore. Based on the detailed conformational studies, the most stable rotamers have been selected. We have analyzed the descriptors of four antioxidant mechanisms important in free radical scavenging: hydrogen atom transfer, sequential proton loss electron transfer, single electron transfer - proton transfer and transition metal chelation, based on the B3LYP/6-311++G(2d,2p) calculations in vacuum and polar media. The results explain the activity difference between cinnamic acid and its derivatives. The descending order of antioxidant potential is as follows: caffeic > sinapinic ~ ferulic > p-coumaric > o-coumaric > m-coumaric ~ phenol. The results have shown that transisomers indicate higher reactivity than cis- and may be considered as good antioxidants. It has been determined that the highest antioxidant ability is related to the hydroxyl group in para position, supported by planar structure and stability of radical forms. π-Type delocalization of unpaired electron on aromatic ring, double bond and para O-atom is the key to radical stabilization. The ortho-dihydroxy substitution in benzene ring positively influences the ability to neutralize free radicals and makes caffeic acid the antioxidant pharmacophore of hydroxycinnamic acids.